Cytotoxic T lymphocytes (CTLs) have been shown to recognize epitope peptides derived from the tumor-associated antigens (TAAs) found on the major histocompatibility complex (MHC) class I molecule, and then kill the tumor cells. Since the discovery of the melanoma antigen (MAGE) family, many other TAAs have been discovered through immunological approaches (NPL1: Boon T, Int J Cancer 1993 May 8, 54(2): 177-80; NPL2: Boon T & van der Bruggen P, J Exp Med 1996 Mar. 1, 183(3): 725-9). Some of these TAAs are currently undergoing clinical development as immunotherapeutic targets.
In several of these TAAs, epitope peptides that can be recognized by CTLs are identified and their application in immunotherapy for various types of cancer is anticipated (NPL3: Harris C C, J Natl Cancer Inst 1996 Oct. 16, 88(20): 1442-55; NPL4: Butterfield L H et al., Cancer Res 1999 Jul. 1, 59(13): 3134-42; NPLS: Vissers J L et al., Cancer Res 1999 Nov. 1, 59(21): 5554-9; NPL6: van der Burg S H et al., J Immunol 1996 May 1, 156(9) 3308-14; NPL7: Tanaka F et al., Cancer Res 1997 Oct. 15, 57(20): 4465-8; NPL8: Fujie T et al., Int J Cancer 1999 Jan. 18, 80(2): 169-72; NPL9: Kikuchi M et al., Int J Cancer 1999 May 5, 81(3): 439-66; NPL10: Oiso M et al., Int J Cancer 1999 May 5, 81(3): 387-94). Until now, several clinical trials using these TAA-derived CTL epitope peptides have been reported. Unfortunately, many of these clinical trials show a low objective response rate (NPL11: Belli F et al., J Clin Oncol 2002 Oct. 15, 20(20): 4169-80; NPL12: Coulie P G et al., Immunol Rev 2002 October, 188: 33-42; NPL13: Rosenberg S A et al., Nat Med 2004 September, 10(9): 909-15). Therefore, there is still demand for identification of novel CTL epitopes that can be used in cancer immunotherapy.
URLC10 (lymphocyte antigen 6 complex, locus K: which is also described as LY6K; GeneBank Accession Number BC117142 (SEQ ID NO: 36)), has been identified as a gene up-regulated in lung cancer and esophageal cancer by gene expression profile analysis using a genome-wide cDNA microarray containing 27,648 genes (NPL14: Ishikawa N et al., Cancer Res. 2007 Dec. 15; 67(24): 11601-11; PTL1: WO2004/031413; PTL2: WO2009/016691). It has been observed that the expression of URLC10 is particularly up-regulated in 80% or more of tumor cells in lung cancer and esophageal cancer patients, and it is not expressed in normal important organs besides the testis. Further, siRNA-mediated down-regulation of the URLC10 expression has been shown to cause suppression of cell proliferation in lung cancer cell lines and esophageal cancer cell lines (NPL14 and PTL2).
Recently, URLC10-derived HLA-A24-restricted CTL epitope peptides (NPL15: Suda T et al., Cancer Sci. 2007 Sep. 2; 98(11): 1803-08; PTL3: WO2006/090810) and HLA-A2-restricted CTL epitope peptides (PTL4: WO2008/102557) have been identified. These peptides are effective in cancer patients having the HLA-A24 type or HLA-A2 type, but cannot be expected to have effect on cancer patients who do not have these HLA types.